Dimethyl Sulfoxide → methyl (3RS,4RS)-4-[3-oxo-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2,5-difluorophenylsulfanyl)ethyl]piperidine-3-acetate

Participants

Reaction Conditions

Reaction Steps

1.88 cm3 of dimethyl sulfoxide in 6 cm3 of dichloromethane are poured, over 10 minutes, over a solution of 1.32 cm3 of oxalyl dichloride in 30 cm3 of dichloromethane cooled to −70° C., with stirring and under an inert atmosphere. After 10 minutes, a solution of 1.7 g of methyl (3RS,4RS)-4-[3-(R,S)-hydroxy-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2,5-difluorophenylsulfanyl)ethyl]piperidine-3-acetate in 15 cm3 of dichloromethane is poured in 10 minutes. After 15 minutes, 8.4 cm3 of triethylamine in 10 cm3 of dichloromethane are added dropwise over 15 minutes and the reaction medium is stirred for 45 minutes in the region of −70° C. and then for 20 hours in the region of 20° C. 50 cm3 of distilled water are poured over the reaction mass, and the organic phase is separated after settling out, and washed with 50 cm3 of a saturated aqueous sodium hydrogen carbonate solution, with 2 times 30 cm3 of distilled water and with 30 cm3 of saturated aqueous sodium chloride solution. The organic extract is dried over magnesium sulfate, filtered, and evaporated under reduced pressure (2 kPa) at a temperature in the region of 40° C. The residue obtained is purified by chromatography under an argon pressure of 50 kPa, on a column of silica gel (particle size 40–60 μm; diameter 3 cm), eluting with a mixture of cyclohexane-ethyl acetate (60/40 by volume) and collecting fractions of 10 cm3. The fractions containing the expected product are pooled and then evaporated according to the conditions described above. 1.37 g of methyl (3RS,4RS)-4-[3-oxo-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2,5-difluorophenylsulfanyl)ethyl]piperidine-3-acetate are obtained.

Provenance & Evidence